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Gene Therapy for HIV
Human immunodeficiency virus (HIV) is a virus that can lead to Acquired Immune Deficiency Syndrome (AIDS). HIV is known as a lentivirus. A lentivirus is a slowly replicating retrovirus (1 ). AIDS is a condition that causes the failure of the immune system which in turn causes pathogens, including opportunistic pathogens, to take advantage of the host's reduced immune system. HIV is transmitted from bodily fluids including semen, blood, and breast milk, and is transmitted by actions like unprotected sexual contact, the use of infected needles and other ways of direct blood contact, and from mother to baby (2) . Virology HIV first attaches and fuses to the host cell at CD4 and the coreceptor. The viral evnelope fuses with the cellular membrane causing the viral genetic material (RNA) to be released into the cell. Once the virus has fused, reverse transcription occurs. Reverse transcription is the creation of double-stranded DNA (in the case of HIV) from an RNA template. The newly synthesized single-stranded DNA then integrates into the nucleus of the host cell. The host cell then transcribes its own DNA with the viral DNA in it as well by RNA polymerase II, causing the viral transcripts to be translated. This translation then causes the assemble, budding, and maturation of the premature virons that proceed to mature (3). HIV-1 infects resting memory CD4+T cells, macrophages, or mononuclear cells. Many of the HIV-1 infected patients experience AIDS progression due to the decline of CD4+T lymphocytes. CD4 (cluster of differentiation 4) is a glycoprotein found on the surface of immune cells (4). HIV-1 uses this specific glycoprotein to gain access into the T-cells. T-cells consist of many types ranging from helper to cytotoxic, but only the types of T cells that contain the CD4 glycoprotein can be infected by HIV-1 (helper, memory, some regulatory). T cells are involved in cell-mediated immunity. When an individual is infected with HIV-1, the number of T cells with the CD4 glycoprotein reduces. Because HIV-1 infects these types of cells, the host's immunity decreases, thus resulting in AIDS, an immune deficiency. HIV Gene Therapy In the attempt to prevent a further decrease in the number of functioning CD4 T cells, scientists of Sangamo BioSciences have engineered immune cells to control HIV. This specific therapy focuses on the CCR5 receptors on the surface of the cells that contain the CD4 glycoprotein. Aforementioned, HIV binds to the cells with CD4. If the binding of the CD4 glycoprotein is inhibited, HIV's pathogenesis can be inhibited. The CCR5 receptors are expressed by two different genes. The scientists of Sangamo BioSciences obtained blood from HIV patients who lacked both of the functioning CCR5 receptor genes. They then knocked out the second CCR5 receptor gene, and then the genetically engineered cells were reinfused into the body (5). Unfortunately, some of the participants (three of the seven) had to be excluded from the experiment because they had low levels of the HIV virus that attaches to both the CCR5 receptors and the CXCR4 receptors. The treatment would not help these individuals because the treatment only works for a strain of the virus that only uses CCR5 receptors. Three of the remaining seven patients (minus the three other participants who had the virus which had both CCR5 and CXCR4 receptors) achieved an undetectable viral load. Two other patients only achieved a transient undetectable status. The treatment increased the CD4 cells. This increase was attributed to the drop in the viral reservoir. The viral reservoir was determined by the total HIV DNA in peripheral blood mononuclear cells (5). Bibliography (1) http://www.nature.com/nature/journal/v322/n6075/abs/322130a0.html (2) http://www.aids.org/topics/aids-faqs/how-is-hiv-transmitted/ (3) http://www.sciencedirect.com/science/article/pii/S1386653205002374 (4) http://en.wikipedia.org/wiki/CD4#Disease (5) http://www.aidsmeds.com/articles/Sangamo_genetics_1667_24579.shtml